The primary goal of this proposal is to establish the chromosomal organization of the human procollagen genes. Up to date, at least five genetically distinct types of collagen have been identified: (a) Type I present mainly in skin, bones and tendons; (b) Type II major consituent of cartilage; (c) Type III found together with Type I in lung, liver, skin and vessels; and, (d) Types IV and V consituents of the basement membrane. All the different types are heterotrimers constituted of identical or similar Alpha-chains which are synthesized as precursor molecules with N- and C-propeptides (procollagens). The different Alpha-chains contain approximately 1000 residues and have a similar primary structure with the repeated amino acidic triplet -Gly, X, Y. Structural and functional features suggest that these nine (or more) genes may have evolved by multiple duplication from a common ancestral unit. These proteins are involved in human connective tissue inherited diseases such as: osteogenesis imperfecta, chondrodystrophies Marfan and Ehlers-Danlos syndrome. It is, therefore, of importance to establish the chromosomal organization of these genes, their linkage at the molecular level, and their association with other sequences in order to have a better understanding of their evolution, ontogenesis, tissue-specific distribution and expression in normal and pathological states. To achieve this goal we propose first to localize the procollagen genes using cloned cDNA specific for the proAlpha-chains of the different types. Second, to isolate from phage libraries collagen-like genes using cDNA and genomic probes under relaxed conditions of hybridization. Third, to establish the linkage among the different genes within a given cluster. Fourth, to characterize the genes with respect to their transcriptional boundaries, to flanking regulatory signals to their association with other genomic sequences which may play a role in their expression.